Causes of panagglutination on the pretransfusion antibody screen

Cause of panagglutination	Findings	Approach to identifying crossmatch compatible blood
Alloantibody to a high-frequency antigen	History of previous exposure to allogeneic RBCs* Negative autocontrol Similar intensity of reactivity to all panel RBCs	Extended phenotype (or genotype) of patient RBCs^¶ If a high-frequency antigen is suspected based on RBC phenotype/genotype, test with panel cells lacking that antigen
Multiple alloantibodies	History of previous exposure to allogeneic RBCs* Negative autocontrol Variable intensity of reactivity to different panel RBCs	Extended phenotype (or genotype) of patient RBCs^¶ Enzyme treatment (papain or ficin) Adsorption and elution
Autoantibodies	Known history of AIHA Positive autocontrol	Direct antiglobulin (direct Coombs) test
Treatment with a therapeutic monoclonal antibody Anti-CD38 Anti-CD47	Documentation of treatment by history or medical record May cause positive autocontrol	Type and screen before starting therapeutic monoclonal antibody For daratumumab, certain in vitro reagents can be used to decrease interference (refer to UpToDate for details)

Panagglutination refers to an antibody screen (indirect antiglobulin test; indirect Coombs test) in which the patient's serum/plasma reacts with all reagent RBCs on the test panels. The autocontrol determines whether the panagglutinin is present in the patient's serum/plasma. A key concern with autoantibodies is that there may also be alloantibodies that are not detected due to panagglutination caused by the autoantibodies. Intravenous immune globulin (IVIG) and anti-RhD do not cause panagglutination since they only contain certain antibodies.

RBCs: red blood cells; AIHA: autoimmune hemolytic anemia.

* The two most common types of exposure are prior transfusion and pregnancy. Rarely, an individual may be exposed via sharing of needles or other types of exposure.

¶ RBC genotyping may not be available in all centers. When available, it is most helpful when commercial reagents are unavailable to test a specific antigen or when RBC phenotyping is inconclusive or especially complex.

Graphic 142066 Version 2.0

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Causes of panagglutination on the pretransfusion antibody screen